Reflections on the Withdrawal of Vioxx from the Market

Three years ago, at a journal club presentation at our hospital and on the hospital web site, I expressed my opinion that the data then available suggesting an excess cardiovascular risk from use of Vioxx (rofecoxib) were inconclusive. I based this opinion on the following. The data compared a large dose of Vioxx (50 mg daily) with a common dose of naproxen. Moreover, the added protective effect the naproxen provided that Vioxx did not provide was not duly taken into account . I believed it possible that the cardiac events reported were not due to the drug but rather to possible misuse of the drug.

Several subsequent research papers have pointed in the same direction but have also been flawed. One example was a recent large-scale epidemiological study suggesting that most nonsteroidal anti-inflammatory drugs increase cardiovascular risk above normal, but that Vioxx, as used in the community (dose not specified, concomitant use of aspirin not specified), increased the risk of heart attack somewhat more than did the other drugs. The reported risk was not great and was maximal within the first 90 days of taking the drug.

Results from the most recent study, the one which led Merck to withdraw Vioxx from the market, were not available until this week. These too were reported to show an excess cardiac risk, approximately double the normal risk, and, inexplicably, occurring not within 90 days of first taking Vioxx, but after 18 months of continuous use. This timeframe introduces more questions. The study, however, was prospective and the data appear to be the most valid of the data available to date. Based on the results of this study as reported, I now must conclude it likely that Vioxx presents increased cardiovascular risk as compared with some of the other nonsteroidals. Clearly, I no longer endorse use of Vioxx.

When the story of the withdrawal of Vioxx from the market broke, I was interviewed by Ms. Gina Kolata of the New York Times, whose article was published on October 1, 2004. The following is a partial quote from her article. It accurately reflects my current opinion.

But others, including Dr. Michael Lockshin, an arthritis specialist at the Hospital for Special Surgery in New York, were less certain. Dr. Lockshin said that, until now, “the data were quite minor” to indicate that Vioxx was causing a problem. The original study’s findings had an alternative explanation, he said, and the other studies were complicated by the fact that they lacked enough rigor to make the case.

The new data, however, convinced him. Even if Merck had not withdrawn the drug, he would no longer prescribe it, Dr. Lockshin said. “Although the numbers are not huge in terms of risk, these are the things that I, looking at it as a practitioner, couldn’t say, ‘Oh, well. This drug is as safe as another.’ “

He added, however, that some of his patients might have difficulty finding an alternative to Vioxx. Pain relief, he said, is idiosyncratic and unpredictable. “Some patients respond beautifully to one drug and not to another.”

See the complete article on the Hospital for Special Surgery’s web site

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